The primary diagnosis of CD30-positive tumour diseases is currently carried out on an immunohistological basis, with only reagents from mice e.g. Ber-H2 being used at present as the antibody. This reagent is a monoclonal antibody directed at the CD30 molecule which was described in 1987 in a short article and in 1989 more detailed (Schwarting et al., Ber-H2; a new anti-Ki-1 (CD30) monoclonal antibody directed at a formol-resistant epitope, Blood, 74:1678-1689, 1989). This antibody is secreted by the mouse myeloma hybrid cell line of the same name. However, it is a considerable disadvantage, in the mass production of this antibody in a long-term culture (in fermenters, for example), that the antibody-producing cells are often, after just a few generations, overgrown by cells which have lost the ability to produce antibodies, obviously because the latter are no longer able to synthesise heavy immunoglobulin chains or also heavy and light immunoglobulin chains.
The propagation diagnosis of the tumour diseases mentioned above is generally carried out by computer tomography, sonography and/or lymphography. The non-invasive propagation diagnosis mentioned, however, is associated with the disadvantage that only relatively large tumour masses can be identified, but that smaller tumours or metastases are not detectable. The surgical propagation diagnosis methods that are therefore often used in addition are a major burden on the patient and are limited to particular body cavities (e.g. abdominal cavities). The standard treatment of CD30-positive tumours which is currently the only medically accepted treatment and thus the only treatment used is carried out using non-specific radio and/or chemotherapy. Although the success rate is approx. 60-70%, there is so far no curative concept for those for whom therapy fails.
For this reason, the monoclonal antibody Ber-H2 was conjugated with vegetable toxins and used experimentally for the treatment of patients with Hodgkin's disease in the terminal phase of the disease (Falini et al., Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin, Lancet, 339:1195-1196, 1992). The four patients treated showed a reduction in tumour mass of 50% to almost 100% within ten days. However, in all cases, after a varying amount of time, the tumours reappeared at the old and/or new locations. It was not possible to repeat the immunotoxin application because the patients, without exception, had already formed antibodies against the mouse antibody Ber-H2.
As such, immunotoxins have already been used experimentally in vivo in humans which have enabled Hodgkin's lymphoma cells to be recognised or eliminated (e.g. Falini et al., Response of refractory Hodgkin's disease to monoclonal anti-CD30 immunotoxin, Lancet, 339:1195-1196, 1992; Falini et al., In vivo targeting of Hodgkin and Reed-Stemberg cells of Hodgkin's disease with monoclonal antibody Ber-H2(CD30): Immunohistological evidence, Brit. J. Haematol., 82:38-45, 1992).
Further, it has been possible to show that the CD30 molecule is expressed in vitro and in vivo selectively by activated TH2 blasts (Romagnani S., Induction of TH1 and TH2 responses: a key role for the ‘natural’ immune response?, Immunol. Today, 13:379-381, 1992) (Del Prete et al., CD30 Th2 cytokines and HIV infection: a complex and fascinating link, Immunol. Today, 16:76-80, 1995). In patients with allergic diseases, the number of CD30+ TH2 blasts was much higher than in normal people. It is therefore conceivable that a majority of autoaggressive diseases are due to a miscontrol of the TH response with an increase in the number of TH2 cells. Thus it should also be possible to use the CD30 molecule as a target in the diagnosis and/or treatment of inflammatory diseases.
However, there remains a need for improved CD30 molecules for use in, e.g., diagnosis and treatment.